U.S. Pat. No. 5,856,336 claimed quinoline type mevalonolactones, specifically pitavastatin. The disclosed process involves the usage of expensive reagents like sodium hydride, n-butyl lithium and borane derivatives, reagents that are difficult to use on a commercial scale.
International publication WO 95/11898 claims a process for the preparation of condensed pyridine type mevalonolactone intermediates using wittig reagent. In the said process the triphenyl phosphonium bromide intermediate compound of formula-7 was condensed with tertiary butyl 2-((4R,6S)-6-formyl-2,2-dimethyl-1,3-dioxan-4-yl)acetate compound of formula-8 in presence of n-BuLi. And the said patent discloses a process for the preparation of lactone intermediate but the conversion of lactone intermediate to pitavastatin calcium salt has not been disclosed. The usage of bases like n-BuLi is not recommendable for commercial scale up processes. Hence this process is commercially not a viable process.
International publication WO 2005/033083 claims process for the preparation of pure 3,5-dihydroxy-6-heptenoic acid derivatives by optical resolution using column separation process, which is not viable of commercial scale.
Other than the above international publication WO 2005/054207 claims process for the preparation of pyrimidine derivatives and its intermediates using wittig reagent; Our international application WO 2007/132482 claims a novel process for the preparation of pitavastatin and its pharmaceutically acceptable salts using wittig reaction. Another international publication WO 2007/125547 claims a process for the preparation of statins free of Z-isomer via julia-olefination.
Polymorphism is the formation of a variety of crystalline forms of the same compound having distinct crystal structures and physical properties like melting points, X-ray diffraction pattern, infrared absorption pattern in fingerprint region, and solid state NMR spectrum. One crystalline form may give rise to thermal behavior different from that of another crystalline form. Different crystalline forms or polymorphs of the same pharmaceutical compounds can and reportedly do have different aqueous solubility. The difference in the physical properties of different crystalline forms results in some forms having distinct advantageous physical properties compared to other crystalline forms of the same compound. The discovery of new polymorphic forms of pharmaceutically useful compounds provides a new opportunity to improve the performance characteristics of a pharmaceutical product. Those skilled in the art can understand that crystallization of an active pharmaceutical ingredient offers the best method for controlling important qualities like chemical quality, particle size, and polymorphic content. There is a need in the art for the preparation of new polymorphic forms of Pitavastatin and its pharmaceutically acceptable salts, and the intermediates which are used in the preparation of pitavastatin and its pharmaceutically acceptable salts.
Accordingly, there remains a need for an improved process for the preparation of pitavastatin and its pharmaceutically acceptable salts that avoids the problems of the prior art, on a commercial scale in a convenient and cost efficient manner.